This review highlights the biosynthesis of heterocycles in polyketide natural products with a focus on oxygen and nitrogen-containing heterocycles with ring sizes between 3 and 6 atoms. Heterocycles are abundant structural elements of natural products from all classes and they often contribute significantly to their biological activity. Progress in recent years has led to a much better understanding of their biosynthesis. In this context, plenty of novel enzymology has been discovered, suggesting that these pathways are an attractive target for future studies.

C4: The domain AmbDH3 from ambruticin biosynthesis catalyses the dehydration of 25 and subsequent cyclisation to tetrahydropyran 27 with high stereoselectivity [15].

Mentions:
1.1.1 oxa-Michael addition: The oxa-Michael addition on an α,β-unsaturated thioester intermediate leads to oxygen heterocycles along with the formation of up to two new stereocentres. Its appearance in several polyketide biosynthetic pathways was proposed for a decade based on gene cluster analysis. An in vitro characterisation of responsible catalytic units has however only recently been achieved. Two pyran-forming cyclase domains were characterised in the pederin (24) and the ambruticin (28) biosynthetic pathways (Scheme 3 and Scheme 4) [14–15].

C4: The domain AmbDH3 from ambruticin biosynthesis catalyses the dehydration of 25 and subsequent cyclisation to tetrahydropyran 27 with high stereoselectivity [15].

Mentions:
1.1.1 oxa-Michael addition: The oxa-Michael addition on an α,β-unsaturated thioester intermediate leads to oxygen heterocycles along with the formation of up to two new stereocentres. Its appearance in several polyketide biosynthetic pathways was proposed for a decade based on gene cluster analysis. An in vitro characterisation of responsible catalytic units has however only recently been achieved. Two pyran-forming cyclase domains were characterised in the pederin (24) and the ambruticin (28) biosynthetic pathways (Scheme 3 and Scheme 4) [14–15].

This review highlights the biosynthesis of heterocycles in polyketide natural products with a focus on oxygen and nitrogen-containing heterocycles with ring sizes between 3 and 6 atoms. Heterocycles are abundant structural elements of natural products from all classes and they often contribute significantly to their biological activity. Progress in recent years has led to a much better understanding of their biosynthesis. In this context, plenty of novel enzymology has been discovered, suggesting that these pathways are an attractive target for future studies.